NM_014424.5:c.57C>T

Variant names:

• chr1-16017907-G-A
• rs945416
• NM_014424.5:c.57C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014424.5(HSPB7):​c.57C>T​(p.Ser19Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 1,613,376 control chromosomes in the GnomAD database, including 284,168 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (28782 hom., cov: 35)
  • Exomes 𝑓: 0.59 (255386 hom.)
• Consequence: HSPB7 NM_014424.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 25 publications found

Genes affected

HSPB7 (HGNC:5249): (heat shock protein family B (small) member 7) This gene encodes a small heat shock family B member that can heterodimerize with similar heat shock proteins. Defects in this gene are associated with advanced heart failure. In addition, the encoded protein may be a tumor suppressor in the p53 pathway, with defects in this gene being associated with renal cell carcinoma. [provided by RefSeq, Mar 2017]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-1.83 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014424.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPB7	NM_014424.5	MANE Select	c.57C>T	p.Ser19Ser	synonymous	Exon 1 of 3	NP_055239.1
	HSPB7	NM_001349689.2		c.57C>T	p.Ser19Ser	synonymous	Exon 1 of 3	NP_001336618.1
	HSPB7	NM_001349683.2		c.57C>T	p.Ser19Ser	synonymous	Exon 1 of 3	NP_001336612.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPB7	ENST00000311890.14	TSL:1 MANE Select	c.57C>T	p.Ser19Ser	synonymous	Exon 1 of 3	ENSP00000310111.9
	HSPB7	ENST00000487046.1	TSL:1	c.57C>T	p.Ser19Ser	synonymous	Exon 1 of 3	ENSP00000419477.1
	HSPB7	ENST00000406363.2	TSL:1	c.57C>T	p.Ser19Ser	synonymous	Exon 1 of 3	ENSP00000385472.2

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92772 AN: 152084 Hom.: 28761 Cov.: 35

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.622

GnomAD2 exomes AF: 0.576 AC: 142795 AN: 248018 AF XY: 0.581

Gnomad AFR exome AF: 0.686

Gnomad AMR exome AF: 0.392

Gnomad ASJ exome AF: 0.510

Gnomad EAS exome AF: 0.752

Gnomad FIN exome AF: 0.566

Gnomad NFE exome AF: 0.592

Gnomad OTH exome AF: 0.570

GnomAD4 exome AF: 0.589 AC: 860908 AN: 1461174 Hom.: 255386 Cov.: 50 AF XY: 0.590 AC XY: 428533 AN XY: 726860

African (AFR) AF: 0.699 AC: 23410 AN: 33470

American (AMR) AF: 0.403 AC: 18005 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 13456 AN: 26132

East Asian (EAS) AF: 0.728 AC: 28894 AN: 39692

South Asian (SAS) AF: 0.586 AC: 50507 AN: 86234

European-Finnish (FIN) AF: 0.565 AC: 30059 AN: 53220

Middle Eastern (MID) AF: 0.610 AC: 3515 AN: 5760

European-Non Finnish (NFE) AF: 0.591 AC: 656667 AN: 1111614

Other (OTH) AF: 0.603 AC: 36395 AN: 60360

GnomAD4 genome AF: 0.610 AC: 92833 AN: 152202 Hom.: 28782 Cov.: 35 AF XY: 0.604 AC XY: 44954 AN XY: 74400

African (AFR) AF: 0.688 AC: 28596 AN: 41552

American (AMR) AF: 0.489 AC: 7469 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1769 AN: 3466

East Asian (EAS) AF: 0.774 AC: 4005 AN: 5174

South Asian (SAS) AF: 0.596 AC: 2876 AN: 4824

European-Finnish (FIN) AF: 0.556 AC: 5895 AN: 10602

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40249 AN: 67976

Other (OTH) AF: 0.621 AC: 1313 AN: 2116

Alfa AF: 0.590 Hom.: 25134

Bravo AF: 0.605

Asia WGS AF: 0.638 AC: 2219 AN: 3478

EpiCase AF: 0.588

EpiControl AF: 0.593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.3
DANN	Benign	0.92
PhyloP100		-1.8
PromoterAI		-0.14	Neutral
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs945416; hg19: chr1-16344402; COSMIC: COSV58893094; COSMIC: COSV58893094;